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Pyruvate Dehydrogenase Kinase 4 Mediates Sex Specific Outcomes In Sepsis Induced Cardiomyopathy, John Yap Jun 2025

Pyruvate Dehydrogenase Kinase 4 Mediates Sex Specific Outcomes In Sepsis Induced Cardiomyopathy, John Yap

Dissertations

During sepsis, males often experience worse cardiac outcomes than females. Here, we identified pyruvate dehydrogenase kinase 4 (PDK4) as a key contributor to this disparity. PDK4 is a mitochondrial protein that regulates glucose utilization by inhibiting pyruvate dehydrogenase (PDH). Using a mouse model of endotoxemia, we induced acute inflammation with a sublethal dose of lipopolysaccharide (LPS), which caused cardiac dysfunction and significantly increased myocardial PDK4 expression in males but not females. Cardiac-specific PDK4 overexpression promoted LPS-induced cardiac dysfunction in both sexes, whereas cardiac-specific PDK4 knockout provided protection. In wild-type males, LPS disrupted cardiac metabolism by decreasing PDH activity and fatty …


Targeting Eya1 Phosphatase Activity In Mll-Rearranged Leukemia, Lola Badmus Jun 2025

Targeting Eya1 Phosphatase Activity In Mll-Rearranged Leukemia, Lola Badmus

Dissertations

MLL-rearranged (MLL-r) leukemia is an aggressive subset of acute leukemia, accounting for up to 10% of adult and 70% of infant AML and ALL cases. These leukemias are driven by MLL fusion proteins, which recruit epigenetic cofactors to dysregulate gene expression, leading to poor prognosis and resistance to conventional chemotherapy. Previous lab work identified EYA1’s role in leukemogenesis, establishing it as a therapeutic target in MLL-r leukemia. EYA1, is a transcriptional coactivator and protein tyrosine phosphatase (PTP). Originally a gout medication, benzbromarone (BBR), was identified in an NCI Diversity Set screen as an EYA1-specific PTP inhibitor. BBR provides a tool …


Interrogating The Dispersal Process And Relevant Genes In Vibrio Fischeri, Jeremy Esin Jun 2025

Interrogating The Dispersal Process And Relevant Genes In Vibrio Fischeri, Jeremy Esin

Dissertations

Biofilms are aggregates of bacteria encased in a matrix that shields bacteria from environmental hazards. These structures are formed in response to cues from the environment and drive colonization of new niches. Biofilms can be both beneficial and detrimental. Largely, research focuses on biofilms that have negative outcomes in clinical, environmental, and economical settings. However, the value of beneficial biofilms is recognized and studied. The marine bacterium Vibrio fischeri is part of a model system for studying symbiotic biofilms in a eukaryotic host. V. fischeri produces a transient biofilm at the surface of a specialized light organ and then disperses …


Benefits And Challenges Of Collaborative Networks Addressing Food System Disruptions During The Covid-19 Pandemic, Dikshya Dahal, Tania Schusler Jun 2025

Benefits And Challenges Of Collaborative Networks Addressing Food System Disruptions During The Covid-19 Pandemic, Dikshya Dahal, Tania Schusler

School of Environmental Sustainability: Faculty Publications and Other Works

The COVID-19 pandemic disrupted food systems with disproportionate impacts on marginalized social groups, which in the USA included racial and ethnic minorities, working class families, immigrants, seniors, and people with disabilities, among others. The pandemic also greatly affected the operations of nonprofit organizations, which play important roles in disaster response. We explored how social networks supported non-profit organizations’ efforts to address increased food insecurity and food-related business disruptions during the pandemic in the Chicago region, IL, USA. We used mixed methods including a Social Network Analysis (SNA) of 48 organizations and their reported partners plus focus group discussions with representatives …


Nazor V. Sydney Sol Group, Ltd. Jun 2025

Nazor V. Sydney Sol Group, Ltd.

All Decisions

In this loft tenant action, the court modified the lower court's order, reinstating claims for rent overcharge, unjust enrichment, and breach of warranty of habitability. The court held that court-ordered use and occupancy payments are not "voluntarily paid" rent under MDL § 302(b), allowing these claims to proceed in a related action. The court also reinstated a claim for accounting of the security deposit and attorneys' fees, finding the landlord failed to prove non-commingling. However, claims for harassment, retaliatory eviction, and constructive eviction were dismissed.


Plasma Insulin-Like Growth Factor-Binding Protein-7 Is Positively Associated With Age, Obesity, Mortality, And Cancer In Postmenopausal Women, Melissa C Orenduff, Carl F Pieper, Emma H Allott, Michael F Coleman, Su Yon Jung, Mara Z Vitolins, Jenifer I Fenton, Chu Chen, Candyce H Kroenke, Fred K Tabung, Ana Barac, Electra D Paskett, Michael N Pollak, Jennifer Hays-Grudo, Shine Chang, Stephen D Hursting Jun 2025

Plasma Insulin-Like Growth Factor-Binding Protein-7 Is Positively Associated With Age, Obesity, Mortality, And Cancer In Postmenopausal Women, Melissa C Orenduff, Carl F Pieper, Emma H Allott, Michael F Coleman, Su Yon Jung, Mara Z Vitolins, Jenifer I Fenton, Chu Chen, Candyce H Kroenke, Fred K Tabung, Ana Barac, Electra D Paskett, Michael N Pollak, Jennifer Hays-Grudo, Shine Chang, Stephen D Hursting

Faculty, Staff and Student Publications

Background: Predictors of premature death and cancer development are needed to more precisely identify individuals who may warrant preventive intervention. Circulating insulin-like growth factor (IGF)-binding protein-7 (IGFBP7) and, to a lesser extent, the IGFBP7/IGF-1 ratio are emerging biomarkers of renal and cardiovascular morbidity. However, their relationships with aging, obesity, mortality, and cancer risk remain unclear.

Methods: This hypothesis-generating study investigated plasma IGFBP7, IGF-1, and their ratio as predictors of all-cause mortality and the incidence of any cancer (excluding nonmelanoma skin cancer), obesity-related cancer (composite of 13 cancer types), and breast cancer in a large longitudinal cohort of postmenopausal women. We …


Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee Jun 2025

Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee

Faculty, Staff and Student Publications

Interval-based designs represent cutting-edge adaptive methodologies for phase I clinical trials to identify the maximum tolerated dose (MTD). These designs exhibit robust performance comparable to more intricate, model-based designs, and their pretabulated decision rule enables them to be implemented as simply as the conventional algorithm-based designs. In this paper, we introduce the posterior predictive (PoP) design, a novel interval-based design that leverages advanced Bayesian predictive hypothesis testing techniques for dose escalation and de-escalation. Our work moves beyond the existing model-assisted interval-based designs by achieving global optimality in dose transition. Theoretically, the global optimality ensures that the proposed design can consistently …


Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Bruce J Fahr, Alyssa M Brown, Amy E Wiebesiek, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky Jun 2025

Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Bruce J Fahr, Alyssa M Brown, Amy E Wiebesiek, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky

Faculty, Staff and Student Publications

Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. In this study, we describe rezatapopt (PC14586), part of a series of compounds designed to reactivate the p53 Y220C mutant. These compounds restore p53 tumor suppressor function by correcting its conformation and enabling it to bind DNA and activate downstream target genes, thus inducing antiproliferative changes in tumor cells. Our findings are supported by biochemical and structural analysis, in vitro and in vivo transcriptomics, and functional data, revealing the recovery of multiple aspects of the wild-type p53 program. …


Comparison Of Open And Laparo-Endoscopic Repair Techniques For Patients With Bilateral Inguinal Hernias, Divyansh Agarwal, Tina Bharani, Nora Fullington, Lauren Ott, Kortney Hodgson, Daelyn Mcclain, Kaela Blake, Michael Reinhorn Jun 2025

Comparison Of Open And Laparo-Endoscopic Repair Techniques For Patients With Bilateral Inguinal Hernias, Divyansh Agarwal, Tina Bharani, Nora Fullington, Lauren Ott, Kortney Hodgson, Daelyn Mcclain, Kaela Blake, Michael Reinhorn

Department of Surgery Faculty Papers

INTRODUCTION: For primary bilateral inguinal hernias, international guidelines favor a laparoscopic posterior mesh repair due to relatively lower risk of acute and chronic pain, faster recovery, and favorable biomechanical properties compared to open anterior approaches (Lichtenstein, plug and patch, etc.). However, studies comparing open mesh-based bilateral inguinal hernia repairs to bilateral laparoscopic and robotic mesh-based approaches are limited. The Abdominal Core Health Quality Collaborative (ACHQC) registry includes longitudinal data on bilateral inguinal hernia repairs performed via open as well as laparo-endoscopic approaches. We hypothesize that outcomes for bilateral inguinal hernia repair are similar between open and laparo-endoscopic approaches in the …


Marketing De Moda Predictivo E Inclusivo: Estrategias De Segmentación Avanzada Para Audiencias Diversas Con Inteligencia Artificial, Oscar Barroso Huertas Jun 2025

Marketing De Moda Predictivo E Inclusivo: Estrategias De Segmentación Avanzada Para Audiencias Diversas Con Inteligencia Artificial, Oscar Barroso Huertas

GDI. Revista de investigación de Género, Diseño e Innovación

Introducción: El marketing predictivo, impulsado por la inteligencia artificial (IA), está transformando cómo las marcas anticipan las necesidades de sus audiencias. En Moda, la personalización es clave para conectar emocionalmente con los consumidores, pero también es esencial que las marcas sean inclusivas, respetando la diversidad y la privacidad. Este artículo explora cómo las marcas de moda usan el marketing predictivo para segmentar audiencias diversas, garantizando campañas personalizadas e inclusivas. Metodología: Este estudio adopta un enfoque mixto, combinando revisión documental y análisis cualitativo. Se revisan fuentes académicas y casos de marcas que aplican marketing predictivo inclusivo, utilizando tecnologías como machine learning …


Dynamics Of Urban Heat And Green Infrastructure, Yunjae Ock Jun 2025

Dynamics Of Urban Heat And Green Infrastructure, Yunjae Ock

Dissertations and Theses

This dissertation provides a comprehensive analysis of the interaction between urban heat and green infrastructure (GI) in terms of dynamic aspects, spatiotemporal variation across various spatial scales, temporal phases, and socioeconomic contexts. By integrating a national-scale longitudinal analysis, street-level structural assessments, and neighborhood-specific resilience frameworks, this study enhances our understanding of how cities can utilize existing ecological assets to mitigate increasing heat risks while addressing systemic inequities.

Urban areas face unprecedented thermal challenges due to climate change and the urban heat island effect, with marginalized communities disproportionately affected. Although cities are increasingly adopting GI expansion for heat mitigation, significant knowledge …


Comparing Emotional Facial Expressions Produced During Personal Narrative Discourse By People With And Without Aphasia, Chloe K. Houghton Jun 2025

Comparing Emotional Facial Expressions Produced During Personal Narrative Discourse By People With And Without Aphasia, Chloe K. Houghton

Theses and Dissertations

This study investigated the differences in emotional facial expressivity between people with aphasia (PWA) and control participants during emotional discourse tasks. Participants consisted of 26 PWA and 26 control participants from Aphasia Talk Bank who retold a stroke or illness story and an important life event story, totaling 104 video files. Undergraduate research assistants were trained to code emotional facial expressions according to valence, intensity, and duration utilizing a modified Facial Expression Coding System (FACES; Kring & Sloan, 1991). Dependent variables included positive frequency, negative frequency, positive intensity, and negative intensity. Results from this study demonstrate that female participants used …


Culture Harder: Use More Specimen To Increase Methicillin-Resistant Staphylococcus Aureus Culture Yield Relative To Pcr, Arvette E. Mitchell, Arpit P. Patel, Jennifer Dicandilo, Zachary W. Rebollido, Matthew Pettengill Jun 2025

Culture Harder: Use More Specimen To Increase Methicillin-Resistant Staphylococcus Aureus Culture Yield Relative To Pcr, Arvette E. Mitchell, Arpit P. Patel, Jennifer Dicandilo, Zachary W. Rebollido, Matthew Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Methicillin-resistant Staphylococcus aureus (MRSA) causes considerable morbidity and mortality in both community-acquired and healthcare-associated infections, but detecting colonization with MRSA has been shown to improve patient outcomes in certain clinical settings. MRSA colonization detection has been carried out in a variety of ways, with molecular assays having superior sensitivity in most studies relative to culture, but culture is disadvantaged in some comparisons by utilization of low specimen volumes. We compared a commercial molecular assay to both low-volume (10 µl) and high-volume (650 µl) cultures and found that increasing the volume utilized for culture led to the detection of 25% more …


Atomistic Characterization Of Hydration-Dependent Fuel Cell Ionomer Nanostructure: Validation By Vibrational Spectroscopy, Dan J. Donnelly, Moon Young Yang, Nicholas Dimakis, Seung Soon Jang, William A. Goddard Iii, Eugene S. Smotkin Jun 2025

Atomistic Characterization Of Hydration-Dependent Fuel Cell Ionomer Nanostructure: Validation By Vibrational Spectroscopy, Dan J. Donnelly, Moon Young Yang, Nicholas Dimakis, Seung Soon Jang, William A. Goddard Iii, Eugene S. Smotkin

Physics & Astronomy Faculty Publications

The development of Nafion alternatives for fuel cells and electrolyzers requires a fundamental understanding of hydration-dependent ion-exchange site acid/base chemistry. We present here reactive force field (ReaxFF) molecular dynamics (MD) simulations of Nafion at varying molar water/ion-exchange-site ratios (λ), which we correlate to our experimental and density functional theory-based vibrational spectra. ReaxFF describes the formation and breaking of covalent bonds, enabling simulations of proton exchange between sulfonic acid/sulfonate groups and water/hydronium. Our MD simulations determine the λ-dependent equilibrium proportions of protonated and deprotonated sites. We find that protonated sites persist across all λ from 0 to 20, challenging the widely …


Core Grade 7: Principles For Moving From Evidence To Recommendations And Decisions, Gordon Guyatt, Per Olav Vandvik, Alfonso Iorio, Arnav Agarwal, Liang Yao, Prashanti Eachempati, Linan Zeng, Derek K. Chu, Rohan D'Souza, Thomas Agoritsas, M. Hassan Murad, Stefan Schandelmaier, Jamie Rylance, Benjamin Djulbegovic, Victor M. Montori, Monica Hultcrantz, Romina Brignardello-Petersen Jun 2025

Core Grade 7: Principles For Moving From Evidence To Recommendations And Decisions, Gordon Guyatt, Per Olav Vandvik, Alfonso Iorio, Arnav Agarwal, Liang Yao, Prashanti Eachempati, Linan Zeng, Derek K. Chu, Rohan D'Souza, Thomas Agoritsas, M. Hassan Murad, Stefan Schandelmaier, Jamie Rylance, Benjamin Djulbegovic, Victor M. Montori, Monica Hultcrantz, Romina Brignardello-Petersen

Peninsula Dental School

This seventh article in a seven part series presents the Core GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach for moving from evidence to recommendations or policy decisions. Core GRADE users make strong recommendations for an intervention versus a comparator when the desirable consequences clearly outweigh the undesirable consequences, and a conditional (weak) recommendation when the balance is less clear. Primary considerations in deciding on recommendations considering an individual patient perspective include balance of benefits, harms, and burdens; the certainty of evidence; and values and preferences. Secondary considerations, most important from a population perspective, include costs, feasibility, acceptability, and …


Mitral Valve Surgery After Failed Transcatheter Intervention For Mitral Regurgitation: Surgical Techniques, Challenges And Outcomes, Mateo Marin-Cuartas, Syed Zaid, Jörg Kempfert, Michael A Borger, Serdar Akansel, Thilo Noack, David Holzhey, Tsuyoshi Kaneko, Isaac George, Gorav Ailawadi, Robert L Smith, Arnar Geirrson, Ahmed El-Eshmawi, Dimosthenis Pandis, Suzanne De Waha, Nikolaos Bonaros, Fabien Praz, Maurizio Taramasso, Michele De Bonis, Lenard Conradi, Christian Hagl, Nicolas Doll, Mahmoud Wehbe, Alexey Dashkevich, Manuela De La Cuesta, Jagdip Kang, Zara Dietze, Philipp Kiefer, Gilbert H L Tang Jun 2025

Mitral Valve Surgery After Failed Transcatheter Intervention For Mitral Regurgitation: Surgical Techniques, Challenges And Outcomes, Mateo Marin-Cuartas, Syed Zaid, Jörg Kempfert, Michael A Borger, Serdar Akansel, Thilo Noack, David Holzhey, Tsuyoshi Kaneko, Isaac George, Gorav Ailawadi, Robert L Smith, Arnar Geirrson, Ahmed El-Eshmawi, Dimosthenis Pandis, Suzanne De Waha, Nikolaos Bonaros, Fabien Praz, Maurizio Taramasso, Michele De Bonis, Lenard Conradi, Christian Hagl, Nicolas Doll, Mahmoud Wehbe, Alexey Dashkevich, Manuela De La Cuesta, Jagdip Kang, Zara Dietze, Philipp Kiefer, Gilbert H L Tang

Faculty, Staff and Students Publications

Objectives: This review article aims to examine the surgical approach to patients with failed mitral transcatheter edge-to-edge repair (M-TEER), focusing on operative challenges, decision-making and contemporary outcome data. Technical considerations, including device removal and the management of complex mitral valve (MV) anatomy, are discussed.

Methods: We performed a comprehensive literature review and gathered the experience from high-volume centres in the surgical management of failed M-TEER.

Results: MV surgery after failed M-TEER is a complex but increasingly necessary procedure as the use of M-TEER grows. It occurs in up to 6% of patients, with a median age of 70-76 years at …


Marking Tidetime: Mudlarking As Intertidal Performance, Sarah Blissett Jun 2025

Marking Tidetime: Mudlarking As Intertidal Performance, Sarah Blissett

School of Art, Design and Architecture

No abstract provided.


Maternal Loss Of Mouse Nlrp2 Alters The Transcriptome And Dna Methylome In Gv Oocytes And Impairs Zygotic Genome Activation In Embryos, Zahra Anvar, Michael D Jochum, Imen Chakchouk, Momal Sharif, Hannah Demond, Alvin K To, Daniel C Kraushaar, Ying-Wooi Wan, Michael C Mari, Simon Andrews, Gavin Kelsey, Ignatia B Van Den Veyver Jun 2025

Maternal Loss Of Mouse Nlrp2 Alters The Transcriptome And Dna Methylome In Gv Oocytes And Impairs Zygotic Genome Activation In Embryos, Zahra Anvar, Michael D Jochum, Imen Chakchouk, Momal Sharif, Hannah Demond, Alvin K To, Daniel C Kraushaar, Ying-Wooi Wan, Michael C Mari, Simon Andrews, Gavin Kelsey, Ignatia B Van Den Veyver

Center for Medical Ethics and Health Policy Staff Publications

Background: NLRP2 is a subcortical maternal complex (SCMC) protein of mammalian oocytes and preimplantation embryos. SCMC proteins are encoded by maternal effect genes and play a pivotal role in the maternal-to-zygotic transition (MZT), early embryogenesis, and epigenetic (re)programming. Maternal inactivation of genes encoding SCMC proteins has been linked to infertility and subfertility in mice and humans, but the underlying molecular mechanisms for the diverse functions of SCMC proteins, and specifically the role of NLRP2, are incompletely understood.

Results: We profiled the DNA methylome of pre-ovulatory germinal-vesicle (GV) oocytes from Nlrp2-null, heterozygous (Het), and wild-type (WT) female mice and assessed the …


Xbp1s-Edem2 Prevents The Onset And Development Of Hfpef By Ameliorating Cardiac Lipotoxicity, Oveena Fonseka, Rida Raja, Claire Ross, Sanskruti R Gare, Jiayan Zhang, Susanne S Hille, Katharine King, Andrea Ruiz-Velasco, Namrita Kaur, Xinyi Chen, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Zhiyong Zou, Xiangjun Zhao, Cristian Sotomayor-Flores, Derk Frank, Eileithyia Swanton, Martin R Pool, Sara Missaglia, Daniela Tavian, Gabriele G Schiattarella, Tao Wang, Luigi Venetucci, Christian Pinali, Martin K Rutter, Bernard D Keavney, Elizabeth J Cartwright, Tamer M A Mohamed, Oliver J Müller, Wei Liu Jun 2025

Xbp1s-Edem2 Prevents The Onset And Development Of Hfpef By Ameliorating Cardiac Lipotoxicity, Oveena Fonseka, Rida Raja, Claire Ross, Sanskruti R Gare, Jiayan Zhang, Susanne S Hille, Katharine King, Andrea Ruiz-Velasco, Namrita Kaur, Xinyi Chen, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Zhiyong Zou, Xiangjun Zhao, Cristian Sotomayor-Flores, Derk Frank, Eileithyia Swanton, Martin R Pool, Sara Missaglia, Daniela Tavian, Gabriele G Schiattarella, Tao Wang, Luigi Venetucci, Christian Pinali, Martin K Rutter, Bernard D Keavney, Elizabeth J Cartwright, Tamer M A Mohamed, Oliver J Müller, Wei Liu

Center for Medical Ethics and Health Policy Staff Publications

Background: Morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) is increased in metabolic disorders. However, options for preventing and treating these prevalent outcomes are limited. Intramyocardial lipotoxicity contributes to cardiac dysfunction. Here, we investigate the mechanisms underlying EDEM2 (endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2) regulation of cardiac lipid homeostasis and assess strategies that inhibit the incidence and progression of HFpEF.

Methods: Metabolic stress was induced in C57BL/6 male mice using a high-fat diet and Nω-nitro-L-arginine methyl ester. The recombinant adeno-associated virus 9 delivery system was used for loss- and gain-of-function studies. Palmitic acid and oleic acid …


A Novel Cardiomyopathy Phenotype Linked To A Chd7 Missense Variant, In Young Park, Chih-Wei Hsu, Karim Bouazoune, Christina E Espindola, Madeline Hannah Mclaughlin Armond, Cristian Coarfa, Sandra L Grimm, James F Martin, Donna M Martin, Cheryl Lyn Walker Jun 2025

A Novel Cardiomyopathy Phenotype Linked To A Chd7 Missense Variant, In Young Park, Chih-Wei Hsu, Karim Bouazoune, Christina E Espindola, Madeline Hannah Mclaughlin Armond, Cristian Coarfa, Sandra L Grimm, James F Martin, Donna M Martin, Cheryl Lyn Walker

Center for Medical Ethics and Health Policy Staff Publications

Loss of function in the chromatin remodeler CHD7 causes CHARGE syndrome, characterized by variable penetrance and diverse abnormalities. However, establishing genotype-phenotype correlations has been challenging, as most CHD7 inactivating mutations are null alleles. Through CHD7 missense variant analysis at potential phosphorylation sites, we identified T730 (T720 in mice) as a critical residue associated with pathogenesis. Using a CHD7 T730 missense variant (Chd7T720A) and a frameshift null allele (Chd7fs) in a mouse model, we found that Chd7fs/fs mice were non-viable, while Chd7fs/+ mice exhibited haploinsufficiency-related circling behavior. Notably, Chd7fs/T720A mice died before postnatal …


In Situ Structure And Assembly Of The Abc-Type Tripartite Pump Macab-Tolc, Tong Huo, Wenfang Zhang, Zhili Yu, Wei Zheng, Yaoming Wu, Qiuyu Ren, Zekai Wan, Junli Cao, Zhao Wang, Xiaodong Shi Jun 2025

In Situ Structure And Assembly Of The Abc-Type Tripartite Pump Macab-Tolc, Tong Huo, Wenfang Zhang, Zhili Yu, Wei Zheng, Yaoming Wu, Qiuyu Ren, Zekai Wan, Junli Cao, Zhao Wang, Xiaodong Shi

Faculty, Staff and Students Publications

The MacAB-TolC tripartite efflux pump is widely distributed in Gram-negative bacteria, extruding antibiotics and virulence factors that lead to multidrug resistance and pathogenicity. However, the in situ structure and assembly mechanism of MacAB-TolC remain unclear. Here, we resolve the in situ structures of the MacAB-TolC efflux pump in Escherichia coli by electron cryo-tomography and subtomogram averaging. In the cells without antibiotic treatment, we observe a fully assembled MacAB-TolC pump. When Escherichia coli cells are treated with erythromycin, in addition to the tripartite pumps, we also discover the emergence of MacA-TolC subcomplexes without MacB, indicating flexible binding of MacB in the …


Correlations Within And Between Highly Multiplexed Proteomic Assays Of Human Plasma, Mary R Rooney, Jingsha Chen, Christie M Ballantyne, Ron C Hoogeveen, Eric Boerwinkle, Bing Yu, Keenan A Walker, Pascal Schlosser, Elizabeth Selvin, Nilanjan Chatterjee, David Couper, Morgan E Grams, Josef Coresh Jun 2025

Correlations Within And Between Highly Multiplexed Proteomic Assays Of Human Plasma, Mary R Rooney, Jingsha Chen, Christie M Ballantyne, Ron C Hoogeveen, Eric Boerwinkle, Bing Yu, Keenan A Walker, Pascal Schlosser, Elizabeth Selvin, Nilanjan Chatterjee, David Couper, Morgan E Grams, Josef Coresh

Faculty, Staff and Students Publications

Introduction: The number of assays on proteomic platforms has grown rapidly. The leading platforms, SomaScan and Olink, have strengths and limitations. Comparisons of precision on the latest platforms-SomaScan 11k and Olink Explore HT-have not yet been established.

Methods: Among 102 participants in the Atherosclerosis Risk in Communities Study (mean age 74 years, 53% women, 47% Black), we used split plasma samples to measure platform precision. CV and Spearman correlations were calculated for each assay. Cross-platform agreement was assessed for overlapping proteins.

Results: SomaScan 11k demonstrated a median correlation of 0.85 for the 10 778 assays and a median CV of …


A Meta-Analysis And Systematic Review Of Cardiac Troponin I Vs T In Community Dwelling Adults: Is Specificity At Risk?, Yashika Parashar, Aya Awwad, Soahum Bagchi, Brian Claggett, Saman Asad Siddiqui, Ajari Winifred Ogheneochuko, Christie M Ballantyne, Christopher Defilippi Jun 2025

A Meta-Analysis And Systematic Review Of Cardiac Troponin I Vs T In Community Dwelling Adults: Is Specificity At Risk?, Yashika Parashar, Aya Awwad, Soahum Bagchi, Brian Claggett, Saman Asad Siddiqui, Ajari Winifred Ogheneochuko, Christie M Ballantyne, Christopher Defilippi

Faculty, Staff and Students Publications

Background: Cardiac troponin I and T measured by high-sensitivity assays (hs-cTn) are detectable in most ambulatory adults. Hs-cTnI and T may perform differently for prediction of cardiovascular (CV) events. In adults with myopathies and advanced age, hs-cTnT can lose CV specificity. We undertook a meta-analysis of ambulatory studies measuring hs-cTn to determine whether hs-cTnI is a superior predictor of CV outcomes.

Methods: Articles evaluating hs-cTnI or T for incident heart failure (HF), myocardial infarction (MI), CV, and all-cause death in ambulatory adults were screened. Adjusted HRs were extracted standardized as hs-cTn tertile 3 vs 1. Pooled effects were calculated, and …


Oral Pcsk9 Inhibitors: Can Novel Therapies Overcome Barriers To Effective Ldl-Cholesterol Management?, Christie M Ballantyne, Alberico L Catapano, Khurram Nasir Jun 2025

Oral Pcsk9 Inhibitors: Can Novel Therapies Overcome Barriers To Effective Ldl-Cholesterol Management?, Christie M Ballantyne, Alberico L Catapano, Khurram Nasir

Faculty, Staff and Students Publications

No abstract provided.


Beyond The Surface: Mapping Dde's Metabolic Footprint On Adolescent Obesity, Zhenjiang Li, Shudi Pan, Brittney O Baumert, Jiawen Carmen Chen, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Justin Ryder, Damaskini Valvi, Todd Jenkins, Stephanie Sisley, Xiangping Lin, Scott M Bartell, Thomas H Inge, Stavra Xanthakos, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Sandrah P Eckel, Rob S Mcconnell, Michele A La Merrill, Douglas I Walker, David V Conti, Lida Chatzi Jun 2025

Beyond The Surface: Mapping Dde's Metabolic Footprint On Adolescent Obesity, Zhenjiang Li, Shudi Pan, Brittney O Baumert, Jiawen Carmen Chen, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Justin Ryder, Damaskini Valvi, Todd Jenkins, Stephanie Sisley, Xiangping Lin, Scott M Bartell, Thomas H Inge, Stavra Xanthakos, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Sandrah P Eckel, Rob S Mcconnell, Michele A La Merrill, Douglas I Walker, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Background: Bariatric surgery is an intervention for severe obesity, leading to significant weight loss and metabolic improvements. However, the release of lipophilic chemicals accumulated in adipose tissue during weight loss presents a unique clinical challenge and research opportunity. Dichlorodiphenyldichloroethylene (DDE) is a persistent organic pollutant increasingly recognized as obesogen, while the biological mechanisms through which DDE influences body mass index (BMI) and waist circumference remain underexplored.

Objectives: We aimed to identify metabolic signatures mediating the association between DDE exposure and weight loss by plasma and adipose tissue metabolomics.

Methods: We conducted a longitudinal study involving 60 adolescents with severe obesity …


Adipocyte/Tumor Cell Crosstalk Via Igf-1/Txnip Axis Promotes Malignancy And Endocrine Resistance In Breast Cancer, Amanda Caruso, Felice Maria Accattatis, Cinzia Giordano, Luca Gelsomino, Piercarlo Del Console, Maria Francesca Fiorita, Balazs Gyorffy, Laura Bianchi, Alfonso Carleo, Rossana De Salvo, Bruno M Simões, Robert B Clarke, Lorenzo Memeo, Cristina Colarossi, Eleonora Aiello, Francesco Conforti, Suzanne A W Fuqua, Matilde Todaro, Giorgio Stassi, Catia Morelli, Diego Sisci, Daniela Bonofiglio, Stefania Catalano, Sebastiano Andò, Ines Barone Jun 2025

Adipocyte/Tumor Cell Crosstalk Via Igf-1/Txnip Axis Promotes Malignancy And Endocrine Resistance In Breast Cancer, Amanda Caruso, Felice Maria Accattatis, Cinzia Giordano, Luca Gelsomino, Piercarlo Del Console, Maria Francesca Fiorita, Balazs Gyorffy, Laura Bianchi, Alfonso Carleo, Rossana De Salvo, Bruno M Simões, Robert B Clarke, Lorenzo Memeo, Cristina Colarossi, Eleonora Aiello, Francesco Conforti, Suzanne A W Fuqua, Matilde Todaro, Giorgio Stassi, Catia Morelli, Diego Sisci, Daniela Bonofiglio, Stefania Catalano, Sebastiano Andò, Ines Barone

Faculty, Staff and Students Publications

Background: Despite significant improvements in the outcome of Estrogen Receptor (ER) α-positive breast cancer (BC) following the use of endocrine therapies, resistance remains a major challenge. Clinical studies proved that obesity, in addition to promote BC progression, is associated with a reduced efficacy to these treatments, but mechanisms remain unclear.

Methods: We used co-culture systems followed by validation through an ‘ex vivo’ model of human mammary obese (Ob) adipocytes and obese endocrine-resistant metastatic Patient-Derived Organoids (PDOs). Transcriptomics with MixOmics-MINT and MetaCore Functional Tools along with lentiviral and pharmacological approaches provide insights into mechanisms. Clinical relevance was investigated using public datasets, …


Suggested Vegetable Planting Dates For Utah, Shawn Olsen Jun 2025

Suggested Vegetable Planting Dates For Utah, Shawn Olsen

All Current Publications

This fact sheet provides suggested planting dates for vegetables in various areas throughout Utah. It also identifies resources for starting seeds at home.


Lipoprotein(A) And Heart Failure Among Black And White Participants In Atherosclerosis Risk In Communities Study, Framingham Offspring Study, And Multi-Ethnic Study Of Atherosclerosis: The Pooling Project, Sarah Nomura, Weihua Guan, Yixin Zhang, Geoffrey H Tison, Hiroaki Ikezaki, Margaret R Diffenderfer, Ching-Ti Liu, Ron C Hoogeveen, Christie M Ballantyne, Ernst J Schaefer, Michael Y Tsai Jun 2025

Lipoprotein(A) And Heart Failure Among Black And White Participants In Atherosclerosis Risk In Communities Study, Framingham Offspring Study, And Multi-Ethnic Study Of Atherosclerosis: The Pooling Project, Sarah Nomura, Weihua Guan, Yixin Zhang, Geoffrey H Tison, Hiroaki Ikezaki, Margaret R Diffenderfer, Ching-Ti Liu, Ron C Hoogeveen, Christie M Ballantyne, Ernst J Schaefer, Michael Y Tsai

Faculty, Staff and Students Publications

Background: This study investigated Lp(a) (lipoprotein(a)) levels with heart failure (HF) incidence overall and ejection fraction (EF) subtypes among Black and White participants in a pooled analysis of MESA (Multi-Ethnic Study of Atherosclerosis), FOS (Framingham Offspring Study), and ARIC (Atherosclerosis Risk in Communities Study).

Methods: This study was conducted among 16 771 White and Black participants in ARIC (N=10 347), MESA (N=4150), and FOS (N=2274). Baseline was time of Lp(a) measurement (ARIC Visit 4: 1996-1998; MESA Visit 1: 2000-2002; FOS Cycle 6: 1995-1998). HF with reduced EF (HFrEF) was defined as EF < 50% and ≥50% as HF with preserved EF (HFpEF). Cox proportional hazards regression was used to evaluate associations between Lp(a) (log-transformed continuous, dichotomized at ≥30 mg/dL and ≥50 mg/dL, and quartiles) and HF (overall, HFpEF, HFrEF) in the overall population and stratified by race. Analyses were replicated excluding prior history of myocardial infarction.

Results: There were 2759 HF cases (HFpEF N=859; …


Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso Jun 2025

Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, …


Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy Jun 2025

Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy

Faculty, Staff and Student Publications

Mutations in the TP53 tumor-suppressor gene in human cancer are unique in that 60% to 70% are of the missense variety, resulting in a full-length protein that is often highly expressed in patients' tumors. These missense mutant proteins often exhibit pro-oncogenic activities (referred to as gain of function) in mouse models and human cell lines and correlate with poor cancer prognosis in some cases.